Abstract 1717: SCR-A014, a novel bispecific ADC targeting B7H3 and DLL3 for SCLC therapy, exhibits potent anti-tumor efficacy

Abstract Background: Small cell lung cancer (SCLC) is a most aggressive lung neuroendocrine tumor, accounting for approximately 15% of all lung cancers. Delta-like ligand 3 (DLL3) is an inhibitory Notch ligand that is highly expressed in SCLC and other neuroendocrine tumors but minimally expressed in normal tissues. B7H3, also known as CD276, is a type I transmembrane protein belonging to the B7 family that includes immune checkpoint molecules such as PD-L1, B7-1, and B7-2. DLL3 and B7H3 are highly overexpressed in small cell lung cancer (SCLC) tumor tissues, with limited presence in normal tissues, making them attractive therapeutic targets. Both B7H3 and DLL3 target shows a high positivity rate (80%) in SCLC patient samples. However, the expression levels of DLL3 and B7H3 are not high, most samples are at a 1+ level. Moreover, B7H3 exhibits relatively slow internalization, whereas DLL3 demonstrates rapid internalization. Based on these complementary characteristics, we propose a dual-antibody drug conjugate strategy targeting both B7H3 and DLL3. This innovative approach aims to enhance antitumor efficacy. Methods Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1717.